Q.1 Library Synthesis Core. Q.I7 Personnel: The continuing goal of the Library Synthesis Core (LSC) will be to develop and disseminate chemical methodology and synthesize chemical libraries as described in the project descriptions (section P). The LSC is subdivided between the three projects described in this proposal, though the interactions between project team members and methodology overlap will be quite extensive. Each project subgroup within the LSC will consist of one postdoctoral fellow and two graduate students. In the course of the library synthesis, the project subgroups will be responsible for methods development, library synthesis, and purity assessment. After library synthesis and purity assessment are completed, the libraries will be delivered to the Administrative and Compound Inventory Core (ACIC) for database entry and storage, and ultimately shipped to members of the Chemical Library Consortium (CLC). Within the LSC, the Assistant Director (Aaron Beeler) oversees the day-to-day management of all three projects, interacting with the postdoctoral students, graduate students, and technicians. He is also responsible for ensuring that the synthesis core accomplishes its stated goals, which include: (1) design of libraries for each project;(2) development and validation of methodologies and reaction protocols for generation and purification of chemical libraries;(3) interacting with the analytical services group for library analysis in the assessment of purity;(4) transferring the libraries to the ACIC for storage and maintenance;and (5) interacting with ACIC personnel to implement the biological and community outreach programs. The Organic Synthesis Specialists (OSS) will primarily implement library synthesis based on methodologies developed in the LSC. Information technology systems support within the Library Synthesis Core will be provided by Aruna Jain. This will mainly consist of oversight of the computers and databases used by the LSC. Dayle Acquilano, the Compound Curator, will continue to facilitate transfer of compound collections from the LSC to the ACIC. Placement of orders and other administrative duties will be provided by Paul Ferrari and Sarah Coenen. Q. 1.2 Library Synthesis: Our specific goals in library synthesis will focus on generation of discrete multimilligram quantities of compounds in pure form (>90% analytical purity). 0.1.3 Library Synthesis Core Informatics: The goal of the Synthesis Core Informatics initiative at the CMLD-BU is to develop an integrated electronic research environment software suite for all affiliated scientists. Q.1.4 Synthesis of Libraries Utilizing Current CMLD-BU Methodologies: The LSC will also be responsible for identifying methodologies developed in the CMLD-BU that have not yet been transferred to library synthesis. The following are methodologies that will be adapted to library synthesis by an Organic Synthesis Specialist.